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Superior relapse rate reductions vs Rebif
Significant impact on disability
Superior reductions in T1 Gd+ lesions
Superior reductions in T2 lesion activity
NEDA by Week 96

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SUPERIOR RELAPSE REDUCTIONS vs REBIF AT YEAR 21

OCREVUS reduced relapse rate by nearly half1

SUPERIOR RELAPSE REDUCTIONS vs REBIF AT YEAR 2 (CONTROLLED PERIOD)1

Annualized relapse rate with OCREVUS® (ocrelizumab) vs Rebif
  • 83%/82% of patients treated with OCREVUS were relapse free at the end of the 2-year controlled period vs 71%/72% with Rebif (OPERA I/OPERA II)1

The efficacy and safety of OCREVUS in RMS were studied vs Rebif in 2 double-blind, double-dummy trials evaluating over 1600 patients for 2 years.1,43

ARR THROUGH 10+ YEARS (CONTROLLED AND OPEN-LABEL EXTENSION [OLE] PERIODS)3

Annualized relapse rates compared to those observed in the controlled period

Relapses were defined as new or worsening neurologic symptoms that were attributable to multiple sclerosis, persisted for over 24 hours, were immediately preceded by a stable or improving neurological state for at least 30 days, and were accompanied by objective neurological worsening as defined in the study protocols. Measurements performed at intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only2,43

Limitations of the open-label, uncontrolled study period

Patients in the OLE period successfully completed the controlled period and are subject to continued dropout; they may represent an enriched population. The endpoints measured were not prespecified or powered to conclude statistical significance; they only convey numerical trends. Conclusions regarding the treatment effect of OCREVUS cannot be drawn on the basis of OLE data. Measurements performed at intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only.1,53

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Contraindications
OCREVUS is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reaction to OCREVUS.

Only OCREVUS significantly impacted disability in 3 endpoints across 2 identical RMS trials vs an active comparator1,43

SUPERIOR REDUCTION IN RISK OF CDP vs REBIF (CONTROLLED PERIOD)

  • OPERA I and II (RMS): 2 identical, active comparator-controlled clinical trials vs Rebif in 1656 patients (OCREVUS: OPERA I [n=410], OPERA II [n=417]; Rebif: OPERA I [n=411], OPERA II [n=418]) with RMS treated for 96 weeks. Both studies included patients who had experienced ≥1 relapse within the prior year, or 2 relapses within the prior 2 years, and had an EDSS score between 0 and 5.5. The primary outcome of both studies was annualized relapse rate (ARR) 

Limitations

  • Patients in the OLE period successfully completed the controlled period and are subject to continued dropout; they may represent an enriched population. The endpoints measured were not prespecified or powered to conclude statistical significance; they only convey numerical trends. Conclusions regarding the treatment effect of OCREVUS cannot be drawn on the basis of OLE data.

DISABILITY DATA THROUGH 10+ YEARS1-3

In the controlled period, fewer OCREVUS patients had experienced disability progression than those who started on Rebif3,56

TIME TO ONSET OF 24-WEEK CDP (CONTROLLED AND OLE PERIODS)3,56

During the controlled period, fewer OCREVUS® (ocrelizumab) patients had experienced disability progression than those who started on Rebif
  • Conclusions regarding the treatment effect of OCREVUS cannot be drawn on the basis of OLE data.
  • All patients in the OLE period have been treated with OCREVUS.3

>90% of patients treated with OCREVUS showed no 12-week or 24-week confirmed disability progression in the controlled period1,43

SIGNIFICANT DIFFERENCE IN CDI vs REBIF (CONTROLLED PERIOD)43

  • >20% OF OCREVUS-TREATED PATIENTS SHOWED CONFIRMED DISABILITY IMPROVEMENT (CDI)43

Confirmed disability progression (CDP) was defined as patients with EDSS ≤5.5 who experienced an EDSS increase of ≥1.0. For patients with EDSS >5.5, progression was an EDSS increase of ≥0.5. Disability progression was categorized as confirmed if it was present at 12 or 24 weeks over the treatment period.43

Confirmed disability improvement (CDI) was defined as a reduction from the baseline EDSS score of at least 1.0 point (or 0.5 points if the baseline EDSS score was >5.5) that was sustained for at least 12 weeks in patients with a baseline EDSS score of at least 2.0.43

See the latest data

Explore the latest OCREVUS safety data, including open-label extension data.

View RMS Safety Data

Request information

Speak to an OCREVUS Representative to learn more about OCREVUS.

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Select Important Safety Information

The warnings and precautions for OCREVUS are infusion reactions, and infections, which include respiratory tract infections, herpes, hepatitis B virus (HBV) reactivation, and a warning for progressive multifocal leukoencephalopathy (PML). Additional warnings are possible increased risk of immunosuppressant effects with other immunosuppressants, reduction in immunoglobulins, malignancies, and immune-mediated colitis.

OCREVUS demonstrated superior reductions in mean number of T1 Gd+ lesions over 2 years1

NEAR-COMPLETE SUPPRESSION of T1 Gd+ LESIONS1*

Mean number of T1 Gd+ lesions with OCREVUS® (ocrelizumab) vs Rebif

T1 GD+ LESIONS (CONTROLLED AND OLE PERIODS)3†

Mean number of T1 Gd+ lesions observed in the OLE period were consistent with the controlled period.

Conclusions regarding the treatment effect of OCREVUS (ocrelizumab) cannot be drawn on the basis of OLE data.

*The precise mechanism by which OCREVUS exerts its therapeutic effects in MS is unknown.1
†Relative reductions vs Rebif in T1 Gd+ lesions were observed in the controlled period at each of the intermediate timepoints, Weeks 24, 48, and 96. The measurements performed at these intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only.2,43

Unadjusted controlled and OLE data include the ITT population; clinical cutoff date: November 2022. Number of T1 Gd+ lesions at each timepoint for all patients in the treatment group divided by the total number of brain MRI scans at that timepoint.2,3

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Infusion Reactions
OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis.

OCREVUS demonstrated superior reductions in mean number of T2 lesions over 2 years1

SUPERIOR REDUCTIONS IN MEAN NUMBER OF NEW OR ENLARGING T2 LESIONS1

NEW OR ENLARGING T2 LESIONS (CONTROLLED AND OLE PERIODS)3

Conclusions regarding the treatment effect of OCREVUS (ocrelizumab) cannot be drawn on the basis of OLE data.

‡Relative reductions in T2 lesions were observed in the controlled period at each of the intermediate timepoints, Weeks 24, 48, and 96. The measurements performed at these intermediate timepoints were not prespecified in the statistical testing hierarchy and reflect numerical trends only.2,43

Unadjusted controlled and OLE data include the ITT population; clinical cutoff date: November 2022. Number of new or enlarging T2 lesions relative to preceding scan for all patients in the treatment group at each timepoint for all patients in the treatment group divided by the total number of brain MRI scans at that timepoint.2,3

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Infections
A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients.

NEDA BY WEEK 96 (POST HOC ANALYSIS)2

No evidence of disease activity (NEDA) in the controlled period including re-baselined analysis

Assessment and limitations of NEDA in OPERA I and II

  • The predefined secondary endpoint was not statistically significant, and it was considered nonconfirmatory because it fell below the break in the statistical hierarchy at change in Multiple Sclerosis Functional Composite Scale (MSFCS) score from baseline to Week 962,43
  • Exploratory result based on modified ITT population2,43

Post hoc analysis: re-baselined NEDA data57

Assessment and limitations of re-baselined NEDA in OPERA I and II57

  • During Weeks 48 to 96, the lower frequency of MRI scans compared with other time periods may have influenced the proportions of patients maintaining NEDA
  • Moving into the clinical practice setting, the optimal timing of re-baselining should reflect the anticipated timing for reaching complete DMT efficacy, to give a more reliable indication of subsequent drug failure
  • Conclusions from cross-trial comparisons are limited because of differences including comparators, patient populations, MRI techniques, frequency of assessments, analysis methods, and definitions of NEDA

See the latest data

Explore the latest OCREVUS safety data, including open-label extension data.

View RMS Safety Data

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Speak to an OCREVUS Representative to learn more about OCREVUS.

Contact a Rep

 

ARR=annualized relapse rate; DMT=disease modifying therapy; EDSS=Expanded Disability Status Scale; Gd+=gadolinium-enhancing; ITT=intent-to-treat; MS=multiple sclerosis; OLE=open-label extension; RMS=relapsing multiple sclerosis.

Important Safety Information & Indications

Indications

OCREVUS is indicated for the treatment of:

  • Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
  • Primary progressive MS, in adults.
Contraindications

OCREVUS is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reaction to OCREVUS.

Warnings and Precautions
Infusion Reactions

OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis. In multiple sclerosis (MS) clinical trials, the incidence of infusion reactions in OCREVUS-treated patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to each infusion] was 34-40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of OCREVUS-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization.

Observe patients treated with OCREVUS for infusion reactions during the infusion and for at least one hour after completion of the infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered. For life-threatening infusion reactions, immediately and permanently stop OCREVUS and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

Serious, including life-threatening or fatal, bacterial, viral, parasitic and fungal infections have been reported in patients receiving OCREVUS. An increased risk of infections (including serious and fatal bacterial, fungal, and new or reactivated viral infections) has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies.

A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of OCREVUS-treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS increased the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. OCREVUS was not associated with an increased risk of serious infections in MS patients in controlled trials. Delay OCREVUS administration in patients with an active infection until the infection is resolved.

Respiratory Tract Infections

A higher proportion of OCREVUS-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 43% of patients on placebo and 10% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.

Herpes

In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in OCREVUS-treated patients than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the OCREVUS-treated patients than in the patients on placebo (2.7% vs 0.8%).

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving OCREVUS. Serious herpes virus infections may occur at any time during treatment with OCREVUS. Some cases were life-threatening.

If serious herpes infections occur, OCREVUS should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered.

Hepatitis B Virus (HBV) Reactivation

Hepatitis B reactivation has been reported in MS patients treated with OCREVUS in the postmarketing setting. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with OCREVUS. Do not administer OCREVUS to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment.

Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants

When initiating OCREVUS after an immunosuppressive therapy or initiating an immunosuppressive therapy after OCREVUS, consider the potential for increased immunosuppressive effect. OCREVUS has not been studied in combination with other MS therapies.

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines. OCREVUS may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following OCREVUS therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Progressive Multifocal Leukoencephalopathy (PML)

Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients with MS treated with OCREVUS in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in OCREVUS-treated patients who had not been treated previously with natalizumab, (which has a known association with PML), were not taking any immunosuppressive or immunomodulatory medications, associated with risk of PML prior to or concomitantly with OCREVUS, and did not have any known ongoing systemic medical conditions resulting in compromised immune system function.

JCV infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

At the first sign or symptom suggestive of PML, withhold OCREVUS and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms of PML. Monitoring with MRI for signs consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present.

If PML is confirmed, treatment with OCREVUS should be discontinued.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with OCREVUS treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during OCREVUS treatment and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing OCREVUS therapy in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Malignancies

An increased risk of malignancy with OCREVUS may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in OCREVUS-treated patients. Breast cancer occurred in 6 of 781 females treated with OCREVUS and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines.

Immune-Mediated Colitis

Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving OCREVUS in the postmarketing setting. Some cases of colitis were serious, requiring hospitalization, with a few patients requiring surgical intervention. Systemic corticosteroids were required in many of these patients. The time from treatment initiation to onset of symptoms in these cases ranged from a few weeks to years. Monitor patients for immune-mediated colitis during OCREVUS treatment, and evaluate promptly if signs and symptoms that may indicate immune-mediated colitis, such as new or persistent diarrhea or other gastrointestinal signs and symptoms, occur.

Use in Specific Populations
Pregnancy

There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to OCREVUS. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier.

Lactation

There are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OCREVUS and any potential adverse effects on the breastfed infant from OCREVUS or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving OCREVUS and for 6 months after the last infusion of OCREVUS.

Most Common Adverse Reactions

RMS: The most common adverse reactions in RMS trials (incidence ≥10% and >REBIF) were upper respiratory tract infections (40%) and infusion reactions (34%).

PPMS: The most common adverse reactions in PPMS trials (incidence ≥10% and >placebo) were upper respiratory tract infections (49%), infusion reactions (40%), skin infections (14%), and lower respiratory tract infections (10%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see additional Important Safety Information throughout and click here for full Prescribing Information and Medication Guide.

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